5,316 research outputs found
Exact reconstruction of gene regulatory networks using compressive sensing.
BackgroundWe consider the problem of reconstructing a gene regulatory network structure from limited time series gene expression data, without any a priori knowledge of connectivity. We assume that the network is sparse, meaning the connectivity among genes is much less than full connectivity. We develop a method for network reconstruction based on compressive sensing, which takes advantage of the network's sparseness.ResultsFor the case in which all genes are accessible for measurement, and there is no measurement noise, we show that our method can be used to exactly reconstruct the network. For the more general problem, in which hidden genes exist and all measurements are contaminated by noise, we show that our method leads to reliable reconstruction. In both cases, coherence of the model is used to assess the ability to reconstruct the network and to design new experiments. We demonstrate that it is possible to use the coherence distribution to guide biological experiment design effectively. By collecting a more informative dataset, the proposed method helps reduce the cost of experiments. For each problem, a set of numerical examples is presented.ConclusionsThe method provides a guarantee on how well the inferred graph structure represents the underlying system, reveals deficiencies in the data and model, and suggests experimental directions to remedy the deficiencies
Data based identification and prediction of nonlinear and complex dynamical systems
We thank Dr. R. Yang (formerly at ASU), Dr. R.-Q. Su (formerly at ASU), and Mr. Zhesi Shen for their contributions to a number of original papers on which this Review is partly based. This work was supported by ARO under Grant No. W911NF-14-1-0504. W.-X. Wang was also supported by NSFC under Grants No. 61573064 and No. 61074116, as well as by the Fundamental Research Funds for the Central Universities, Beijing Nova Programme.Peer reviewedPostprin
Augmented Sparse Reconstruction of Protein Signaling Networks
The problem of reconstructing and identifying intracellular protein signaling
and biochemical networks is of critical importance in biology today. We sought
to develop a mathematical approach to this problem using, as a test case, one
of the most well-studied and clinically important signaling networks in biology
today, the epidermal growth factor receptor (EGFR) driven signaling cascade.
More specifically, we suggest a method, augmented sparse reconstruction, for
the identification of links among nodes of ordinary differential equation (ODE)
networks from a small set of trajectories with different initial conditions.
Our method builds a system of representation by using a collection of integrals
of all given trajectories and by attenuating block of terms in the
representation itself. The system of representation is then augmented with
random vectors, and minimization of the 1-norm is used to find sparse
representations for the dynamical interactions of each node. Augmentation by
random vectors is crucial, since sparsity alone is not able to handle the large
error-in-variables in the representation. Augmented sparse reconstruction
allows to consider potentially very large spaces of models and it is able to
detect with high accuracy the few relevant links among nodes, even when
moderate noise is added to the measured trajectories. After showing the
performance of our method on a model of the EGFR protein network, we sketch
briefly the potential future therapeutic applications of this approach.Comment: 24 pages, 6 figure
Inferring Regulatory Networks by Combining Perturbation Screens and Steady State Gene Expression Profiles
Reconstructing transcriptional regulatory networks is an important task in
functional genomics. Data obtained from experiments that perturb genes by
knockouts or RNA interference contain useful information for addressing this
reconstruction problem. However, such data can be limited in size and/or are
expensive to acquire. On the other hand, observational data of the organism in
steady state (e.g. wild-type) are more readily available, but their
informational content is inadequate for the task at hand. We develop a
computational approach to appropriately utilize both data sources for
estimating a regulatory network. The proposed approach is based on a three-step
algorithm to estimate the underlying directed but cyclic network, that uses as
input both perturbation screens and steady state gene expression data. In the
first step, the algorithm determines causal orderings of the genes that are
consistent with the perturbation data, by combining an exhaustive search method
with a fast heuristic that in turn couples a Monte Carlo technique with a fast
search algorithm. In the second step, for each obtained causal ordering, a
regulatory network is estimated using a penalized likelihood based method,
while in the third step a consensus network is constructed from the highest
scored ones. Extensive computational experiments show that the algorithm
performs well in reconstructing the underlying network and clearly outperforms
competing approaches that rely only on a single data source. Further, it is
established that the algorithm produces a consistent estimate of the regulatory
network.Comment: 24 pages, 4 figures, 6 table
Evolutionary constraints on the complexity of genetic regulatory networks allow predictions of the total number of genetic interactions
Genetic regulatory networks (GRNs) have been widely studied, yet there is a
lack of understanding with regards to the final size and properties of these
networks, mainly due to no network currently being complete. In this study, we
analyzed the distribution of GRN structural properties across a large set of
distinct prokaryotic organisms and found a set of constrained characteristics
such as network density and number of regulators. Our results allowed us to
estimate the number of interactions that complete networks would have, a
valuable insight that could aid in the daunting task of network curation,
prediction, and validation. Using state-of-the-art statistical approaches, we
also provided new evidence to settle a previously stated controversy that
raised the possibility of complete biological networks being random and
therefore attributing the observed scale-free properties to an artifact
emerging from the sampling process during network discovery. Furthermore, we
identified a set of properties that enabled us to assess the consistency of the
connectivity distribution for various GRNs against different alternative
statistical distributions. Our results favor the hypothesis that highly
connected nodes (hubs) are not a consequence of network incompleteness.
Finally, an interaction coverage computed for the GRNs as a proxy for
completeness revealed that high-throughput based reconstructions of GRNs could
yield biased networks with a low average clustering coefficient, showing that
classical targeted discovery of interactions is still needed.Comment: 28 pages, 5 figures, 12 pages supplementary informatio
- …